Inflammation and blood-brain barrier breach remote from the primary injury following neurotrauma

Autor: Charlotte Bailey, Melinda Fitzgerald, Marcus K. Giacci, Anna M. B. Black, Alexander Gough, Carole A. Bartlett, Thomas O. Clarke, Nicole M. Smith, Sarah A. Dunlop, Terence McGonigle, K. Swaminathan Iyer
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Pathology
Time Factors
medicine.medical_treatment
Nitric Oxide Synthase Type II
Functional Laterality
lcsh:RC346-429
0302 clinical medicine
Blood-brain barrier
Microglia
General Neuroscience
Microfilament Proteins
Ectodysplasins
medicine.anatomical_structure
Cytokine
Neurology
Optic nerve
Encephalitis
Cytokines
Female
Tumor necrosis factor alpha
medicine.symptom
Secondary degeneration
medicine.medical_specialty
Optic tract
Immunology
Central nervous system
Inflammation
Blood–brain barrier
03 medical and health sciences
Cellular and Molecular Neuroscience
Antigens
CD
medicine
Animals
Visual Pathways
lcsh:Neurology. Diseases of the nervous system
Analysis of Variance
business.industry
Research
Macrophages
Calcium-Binding Proteins
Fibrinogen
Optic Nerve
Rats
Disease Models
Animal
030104 developmental biology
Optic Nerve Injuries
business
Neurotrauma
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-18 (2018)
Journal of Neuroinflammation
ISSN: 1742-2094
Popis: Background Following injury to the central nervous system, increased microglia, secretion of pro- and anti-inflammatory cytokines, and altered blood-brain barrier permeability, a hallmark of degeneration, are observed at and immediately adjacent to the injury site. However, few studies investigate how regions remote from the primary injury could also suffer from inflammation and secondary degeneration. Methods Adult female Piebald-Viral-Glaxo (PVG) rats underwent partial transection of the right optic nerve, with normal, age-matched, unoperated animals as controls. Perfusion-fixed brains and right optic nerves were harvested for immunohistochemical assessment of inflammatory markers and blood-brain barrier integrity; fresh-frozen brains were used for multiplex cytokine analysis. Results Immediately ventral to the optic nerve injury, immunointensity of both the pro-inflammatory biomarker inducible nitric oxide synthase (iNOS) and the anti-inflammatory biomarker arginase-1 (Arg1) increased at 7 days post-injury, with colocalization of iNOS and Arg1 immunoreactivity within individual cells. CD11b+ and CD45+ cells were increased 7 days post-injury, with altered BBB permeability still evident at this time. In the lower and middle optic tract and superior colliculus, IBA1+ resident microglia were first increased at 3 days; ED1+ and CD11b+ cells were first increased in the middle and upper tract and superior colliculus 7 days post-injury. Increased fibrinogen immunoreactivity indicative of altered BBB permeability was first observed in the contralateral upper tract at 3 days and middle tract at 7 days post-injury. Multiplex cytokine analysis of brain homogenates indicated significant increases in the pro-inflammatory cytokines, IL-2 and TNFα, and anti-inflammatory cytokine IL-10 1 day post-injury, decreasing to control levels at 3 days for TNFα and 7 days for IL-2. IL-10 was significantly elevated at 1 and 7 days post-injury with a dip at 3 days post-injury. Conclusions Partial injury to the optic nerve induces a complex remote inflammatory response, characterized by rapidly increased pro- and anti-inflammatory cytokines in brain homogenates, increased numbers of IBA1+ cells throughout the visual pathways, and increased CD11b+ and ED1+ inflammatory cells, particularly towards the synaptic terminals. BBB permeability can increase prior to inflammatory cell infiltration, dependent on the brain region.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje